Chromatographic separation device having improved peak capacity

Abstract

Described are a chromatographic separation device and a method for performing a chromatographic separation. The device two chromatographic separation modules in serial communication. The first module is adapted to receive a gradient includes mobile phase. The second module receives the gradient mobile phase that exits from the first module. The first and second modules include chromatographic sorbents that differ in one or more of composition, particle size and sorbent temperature. The retentivity of the second module is greater than the retentivity of the first module and the chromatographic dispersion of the second module is less than the chromatographic dispersion of the first module. The width of a chromatographic peak eluted from the first module is greater than a width of the same chromatographic peak after elution from the second module. The device has a high peak capacity without the need to pack a full column length with small sorbent particles.

1 . A chromatographic separation device comprising:
 a first chromatographic separation module comprising a first chromatographic sorbent having a first retentivity, a first length and a first chromatographic dispersion;   a second chromatographic separation module configured in serial communication with the first chromatographic separation module to receive a gradient mobile phase therefrom, the second chromatographic separation module comprising a chromatographic sorbent having a second retentivity that is greater than the first retentivity, a second length that is shorter than the first length, and a second chromatographic dispersion that is less than the first chromatographic dispersion, wherein a width of a chromatographic peak in the gradient mobile phase eluted from the first chromatographic separation module is greater than the width of the chromatographic peak in the gradient mobile phase eluted from the second chromatographic separation module.   
     
     
         2 . The device of  claim 1  wherein a sorbent particle size of the first chromatographic separation module is greater than a sorbent particle size of the second chromatographic separation module. 
     
     
         3 . The device of  claim 1  wherein the first chromatographic separation module and the second chromatographic separation module comprise a pair of chromatographic columns in serial communication. 
     
     
         4 . The device of  claim 1  wherein the first and second chromatographic separation modules are formed in a single chromatographic column. 
     
     
         5 . The device of  claim 4  wherein the single chromatographic column is packed with sorbent having a particle size that changes as a gradient along a length of the single chromatographic column. 
     
     
         6 . The device of  claim 5  wherein the sorbent has a retentivity gradient along the length of the single chromatographic column. 
     
     
         7 . The device of  claim 1  wherein at least one of the first and second chromatographic separation modules is a monolithic sorbent. 
     
     
         8 . The device of  claim 1  further comprising a temperature controller in communication with the first and second chromatographic separation modules and configured to maintain a temperature differential therebetween. 
     
     
         9 . A method for performing a chromatographic separation, the method comprising:
 providing a flow of a gradient mobile phase through a first chromatographic separation module having a first retentivity, a first length and a first chromatographic dispersion; and   providing a flow of the gradient mobile phase eluted from the first chromatographic separation module to a second chromatographic separation module having a second retentivity that is greater than the first retentivity, a second length that is shorter than the first length, and a second chromatographic dispersion that is less than the first chromatographic dispersion, wherein a width of a chromatographic peak in the gradient mobile phase eluted from the first chromatographic separation module is greater than a width of the chromatographic peak in the gradient mobile phase eluted from the second chromatographic separation module.   
     
     
         10 . The method of  claim 9  wherein a temperature of the first chromatographic separation module is different from a temperature of the second chromatographic separation module. 
     
     
         11 . The method of  claim 9  wherein providing the flow of the gradient mobile phase eluted from the first chromatographic separation module to the second chromatographic separation module comprises providing a diluted flow of the gradient mobile phase eluted from the first chromatographic separation module to the second chromatographic separation module. 
     
     
         12 . The method of  claim 11  wherein a diluent used to dilute the flow of the gradient mobile phase is a weak mobile phase. 
     
     
         13 . The method of  claim 12  wherein the weak mobile phase is an aqueous solvent. 
     
     
         14 . The device of  claim 1  wherein at least one of the first chromatographic separation module and the second chromatographic separation module is disposed in a microfluidic liquid chromatography system. 
     
     
         15 . The device of  claim 4  wherein the single chromatographic column is disposed in a microfluidic liquid chromatography system. 
     
     
         16 . The method of  claim 9  wherein at least one of the first chromatographic separation module and the second chromatographic separation module is disposed in a microfluidic chromatography system.